A. Field of the Invention
The invention relates primarily to compositions of matter and process for preparation thereof, the compositions of matter comprising an enzyme labeled with a radioactive nuclide. The resulting radioisotope is specifically absorbed by blood clots, thereby providing a method for localizing thromboembolic disorders.
B. Description of the Prior Art
The use of radionuclides as medical diagnostic tools has increased in recent years. As an example, technetium-99m labeled organic chelates, such as are disclosed by Richards et al in U.S. Pat. No. 3,466,361, have been used for scintophotographic scanning in brain tumor localization, thyroid visualization, etc. Technetium-99m exhibits characteristics which render it a desirable radionuclide for medical applications due to a combination of advantageous physical characteristics. Since this radionuclide has a six hour half-life and does not emit beta radiation, millicurie amounts of the substance may be administered to a patient with only minimum radioactivity dosages. The gamma emission of 140 Kev. satisfactorily penetrates tissue while being readily collimated for ease of use with most scanning equipment. A substance containing technetium-99m which clears the blood readily, does not enter metabolic processes, and specifically localizes blood clots would thus be of great benefit in the diagnosis and treatment of thromboembolic disease. Several substances have been proposed in the art for such a use, among them fibrinogen, anti-fibrin, technetium-labeled platelets, and various radioactive particles. The present invention provides inter alia radioactive urokinase, one form of which is labeled with technetium-99m, for specifically localizing blood clots associated with thromboembolic disease. The present compounds exhibit advantages over those substances previously proposed since they are less likely to be antigenetic; they clear the blood stream rapidly; they do not have to be injected prior to clot formation; they are stable; and they can be purified readily and separated from lingering contaminants such as hepatitis virus.